A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials.
We conducted a meta-analysis of pharmacogenomic substudies of three randomized trials conducted in patients with decompensated heart failure (HF) that were led by National Heart Lung and Blood Institute (NHLBI)-funded HF Network to test the hypothesis that candidate genes modulate net fluid loss and weight change in patients with decompensated HF treated with a furosemide-based diuretic regimen. Although none of the genetic variants previously shown to modulate the effects of loop diuretics in healthy individuals were associated with net fluid loss after 72 h of treatment, a set of rare variants in the APOL1 gene, which codes for apolipoprotein L1 (P=0.0005 in the random effects model), was associated with this end point. Moreover, a common variant in the multidrug resistance protein-4 coding gene (ABCC4, rs17268282) was associated with weight loss with furosemide use (P=0.0001). Our results suggest that both common and rare genetic variants modulate the response to a furosemide-based diuretic regimen in patients with decompensated HF.
de Denus, S; Rouleau, JL; Mann, DL; Huggins, GS; Cappola, TP; Shah, SH; Keleti, J; Zada, YF; Provost, S; Bardhadi, A; Phillips, MS; Normand, V; Mongrain, I; Dubé, M-P
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